Methods of treating obesity or diabetes using NT-4/5

Abstract

The invention concerns methods for treating obesity, non-insulin dependent diabetes mellitus, metabolic syndrome, and other related diseases by administering an NT-4/5 polypeptide. The invention also concerns compositions and kits comprising an NT-4/5 polypeptide.

1 . A method for treating obesity in an individual, said method comprising administering to said individual an effective amount of an NT-4/5 polypeptide, wherein the individual does not have genetic deficiency of BDNF.  
     
     
         2 . The method of  claim 1 , wherein the individual has leptin-resistance.  
     
     
         3 . The method of  claim 1 , wherein a disorder associated with obesity is treated in the individual, and the disorder is selected from the group consisting of hyperglycemia, low glucose tolerance, insulin resistance, lipid disorder, dyslipidemia, hyperlipidemia, hypertriglyceridemia, and metabolic syndrome.  
     
     
         4 . The method of  claim 1 , wherein the individual has a reduction of body fat content as a result of the treatment.  
     
     
         5 . The method of  claim 1 , wherein said NT-4/5 polypeptide is a naturally occurring NT-4/5.  
     
     
         6 . The method of  claim 1 , wherein said NT-4/5 polypeptide comprises the amino acid sequence of SEQ ID NO:1.  
     
     
         7 . The method of  claim 1 , wherein said NT-4/5 polypeptide comprises the amino acid sequence of SEQ ID NO:1 with an amino acid substitution.  
     
     
         8 . The method of  claim 1 , wherein said NT-4/5 polypeptide is linked to a polyethylene glycol molecule (PEG).  
     
     
         9 . The method of  claim 8 , wherein said NT-4/5 polypeptide comprises the amino acid sequence of SEQ ID NO:1 with amino acid residue G at position  1  changed to S or T, and wherein said NT-4/5 polypeptide is linked to a PEG molecule at position  1 .  
     
     
         10 . The method of  claim 1 , wherein said NT-4/5 polypeptide is administered in conjunction with an antibody that specifically binds to said NT-4/5 polypeptide.  
     
     
         11 . A method for reducing body weight or preventing weight gain in an individual, said method comprising administering to said individual an effective amount of an NT-4/5 polypeptide, wherein the individual does not have genetic deficiency of BDNF.  
     
     
         12 . The method of  claim 11 , wherein said NT-4/5 polypeptide is a naturally occurring NT-4/5.  
     
     
         13 . The method of  claim 11 , wherein said NT-4/5 polypeptide comprises the amino acid sequence of SEQ ID NO:1.  
     
     
         14 . The method of  claim 11 , wherein said NT-4/5 polypeptide comprises the amino acid sequence of SEQ ID NO:1 with an amino acid substitution.  
     
     
         15 . The method of  claim 11 , wherein said NT-4/5 polypeptide is linked to a polyethylene glycol molecule (PEG).  
     
     
         16 . The method of  claim 15 , wherein said NT-4/5 polypeptide comprises the amino acid sequence of SEQ ID NO:1 with amino acid residue G at position  1  changed to S or T, and wherein said NT-4/5 polypeptide is linked to a PEG molecule at position  1 .  
     
     
         17 . The method of  claim 11 , wherein said NT-4/5 polypeptide is administered in conjunction with an antibody that specifically binds to said NT-4/5 polypeptide.  
     
     
         18 . A method for treating non-insulin dependent diabetes mellitus in an individual comprising administering to said individual an effective amount of an NT-4/5 polypeptide.  
     
     
         19 . The method of  claim 18 , wherein an disorder associated with the non-insulin dependent diabetes mellitus in the individual is treated, and wherein the disorder is selected from the group consisting of hyperglycemia, low glucose tolerance, insulin resistance, abdominal obesity, lipid disorder, dyslipidemia, hyperlipidemia, hypertriglyceridemia, and metabolic syndrome.  
     
     
         20 . The method of  claim 18 , wherein said NT-4/5 polypeptide is a naturally occurring NT-4/5.  
     
     
         21 . The method of  claim 18 , wherein said NT-4/5 polypeptide comprises the amino acid sequence of SEQ ID NO:1.  
     
     
         22 . The method of  claim 18 , wherein said NT-4/5 polypeptide comprises the amino acid sequence of SEQ ID NO:1 with an amino acid substitution.  
     
     
         23 . The method of  claim 18 , wherein said NT-4/5 polypeptide is linked to a polyethylene glycol molecule (PEG).  
     
     
         24 . The method of  claim 23 , wherein said NT-4/5 polypeptide comprises the amino acid sequence of SEQ ID NO:1 with amino acid residue G at position  1  changed to S or T, and wherein said NT-4/5 polypeptide is linked to a PEG molecule at position  1 .  
     
     
         25 . The method of  claim 18 , wherein said NT-4/5 polypeptide is administered in conjunction with an antibody that specifically binds to said NT-4/5 polypeptide.  
     
     
         26 . A method for treating metabolic syndrome in an individual, said method comprising administering to said individual an effective amount of an NT-4/5 polypeptide.  
     
     
         27 . The method of  claim 26 , wherein said NT-4/5 polypeptide is a naturally occurring NT-4/5.  
     
     
         28 . The method of  claim 26 , wherein said NT-4/5 polypeptide comprises the amino acid sequence of SEQ ID NO:1.  
     
     
         29 . The method of  claim 26 , wherein said NT-4/5 polypeptide comprises the amino acid sequence of SEQ ID NO:1 with an amino acid substitution.  
     
     
         30 . The method of  claim 26 , wherein said NT-4/5 polypeptide is linked to a polyethylene glycol molecule (PEG).  
     
     
         31 . The method of  claim 30 , wherein said NT-4/5 polypeptide comprises the amino acid sequence of SEQ ID NO:1 with amino acid residue G at position  1  changed to S or T, and wherein said NT-4/5 polypeptide is linked to a PEG molecule at position  1 .  
     
     
         32 . The method of  claim 26 , wherein said NT-4/5 polypeptide is administered in conjunction with an antibody that specifically binds to said NT-4/5 polypeptide.  
     
     
         33 . A pharmaceutical composition comprising an NT-4/5 polypeptide and a pharmaceutically acceptable excipient, wherein the NT-4/5 polypeptide is linked to a PEG molecule.  
     
     
         34 . The pharmaceutical composition of  claim 33 , wherein the NT-4/5 polypeptide comprises amino acid sequence of a mature NT-4/5 protein with an amino acid substitution, wherein the substituted amino acid is linked to the PEG molecule.  
     
     
         35 . The pharmaceutical composition of  claim 33 , wherein said NT-4/5 polypeptide comprises the amino acid sequence of SEQ ID NO:1 with amino acid residue G at position  1  changed to S or T, and wherein said NT-4/5 polypeptide is linked to a PEG molecule at position  1 .  
     
     
         36 . The pharmaceutical composition of  claim 33 , wherein said NT-4/5 polypeptide comprises the amino acid sequence of SEQ ID NO:1 with amino acid residue S at position  50  changed to C, and wherein said NT-4/5 polypeptide is linked to a PEG molecule at position  50 .